Heart Wall - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 289

6.1.8.8 RNA-Binding Proteins

Cytoplasmic and nuclear RNA-binding proteins (RBP) bind to either double-
(dsRNA) or single-stranded (ssRNA) RNAs using RNA recognition motif (RRM), 31
type-1 and -2 K homology (KH) domains, zinc finger region, RGG (Arg-Gly-
Gly) box, DEAD/DEAH box (associated with RNA helicase activity), Pumilio/FBF
(PUF) domain, double-stranded RNA-binding motif (DSRBD), Piwi/Argonaute/
Zwille (PAZ) sequence (associated with binding to short single-stranded RNAs such
as microRNAs), 32 Sm region (associated with small nuclear snRNA binding), cold-
shock domain (CSD; involved in transcriptional and post-transcriptional regulation),
among others [ 535 , 536 ]. RNA-binding proteins can link to RNAs via RNA bases,
ribose, and phosphate groups.
Many RBPs contain 1 or more copies of a given RNA-binding domain and
auxiliary domains, whereas others have 2 or more different domains. Interdomain
linkers facilitate the recognition of substrates [ 535 ]. RNA-binding modules can
be combined with catalytic domains to regulate the activity of the enzyme. Many
RBPs have modular structures, various modules defining the structural unit; they
are composed of multiple repeats of a small number of basic domains arranged
in different manners that create both RNA-binding and functional diversity [ 535 ].
Combination of a given RNA-binding domain with distinct auxiliary functional
motifs adds further diversity. In addition, RBPs undergo post-translational modifica-
tions, such as phosphorylation, methylation, and sumoylation, which control RNA
binding as well as their function and localization [ 536 ]. Moreover, RNA-binding
proteins can dimerize [ 535 ].
Ribonucleoprotein complexes (RNP) result from association of RNAs with
RNA-binding proteins that have different RNA-sequence specificities and affinities.
In vertebrates, cells encode hundreds to thousands of RBPs, each with unique RNA-
binding activity and between-protein interaction characteristics. A relatively small
number of RNA-binding scaffolds can be involved in RNA processing.
RNA-binding proteins influence the structure and interactions of RNAs.
RNA-binding proteins can be classified according to target RNA types, such as
messenger RNA (mRNA), ribosomal RNA (rRNA), or transfer RNA (tRNA).
Heterogeneous ribonucleoproteins (hnRNP), or pre-mRNPs, and messenger ri-
bonucleoproteins (mRNP) are connected to pre-mRNAs (originally called hnRNAs)
and mRNAs, respectively. Several hnRNPs shuttle between the nucleus and cyto-
plasm, whereas others localize only in the nucleus. They operate in transcription,
stability, function, packaging (i.e., preparing pre-mRNAs for post-transcriptional
processes), transport, localization, processing, and turnover, hence controlling many
post-transcriptional steps in gene expression. In particular, they regulate pre-mRNA

31 A.k.a. RNA-binding domain (RBD) and RNP domain.
32 For example, induced pluripotent stem cell factor Lin28 is a repressor of microRNA processing
and a post-transcriptional regulator of a mRNA set.